The Silent Link: Exploring Why Metformin Causes Vitamin B12 Deficiency?

Metformin, a widely prescribed medication for managing type 2 diabetes, has brought substantial relief to millions of individuals by regulating blood sugar levels. However, its prolonged use has unveiled a hidden consequence – the potential for vitamin B12 deficiency. 

While metformin’s effectiveness in reducing glucose production and improving insulin sensitivity is well-documented, its impact on vitamin B12 absorption remains a matter of concern. So, why metformin causes vitamin B12 deficiency?

This article delves into the intricate relationship between metformin and vitamin B12, shedding light on the mechanisms through which this medication may lead to deficiency. 

Vitamin B12 is essential for neurological function and blood cell formation, and understanding how its levels can be compromised by metformin is crucial for patients and healthcare providers. 

We will explore the underlying biological processes, risk factors, and potential mitigations to help individuals maintain their overall health while managing diabetes with metformin.

Why Metformin Causes Vitamin B12 Deficiency?

Before we delve into why metformin might induce vitamin B12 deficiency, it’s crucial to comprehend the significance of vitamin B12 in the human body. 

Vitamin B12 is essential for the replication and repair of DNA, a fundamental process in cell division and growth. It is crucial for the maturation of red blood cells. A deficiency can led to anemia, resulting in fatigue and weakness.

Vitamin B12 is vital for the health of the nervous system, including the myelin sheath that insulates nerve cells. Deficiency can cause nerve damage and neurological symptoms like numbness and tingling.

Metformin: A Diabetes Game-Changer

Metformin, a medication developed in the 1950s, has become a cornerstone in the management of type 2 diabetes. It is highly effective in controlling blood sugar levels by primarily reducing the production of glucose in the liver and enhancing the body’s response to insulin. 

With minimal risk of hypoglycemia (low blood sugar), it’s often the first-line therapy prescribed to individuals with type 2 diabetes. 

Metformin has significantly improved the lives of those living with diabetes, allowing better control of the condition and reducing the risk of diabetes-related complications.

The Metformin-Vitamin B12 Connection

The association between metformin and vitamin B12 deficiency has been a subject of research and debate for several years. 

The relationship between the two can be traced to the effects of metformin on the gastrointestinal system, where vitamin B12 is primarily absorbed. Here are some key factors contributing to this connection:

Altered Gut Microbiota

Metformin can alter the composition of the gut microbiota. The gut is home to a vast community of microorganisms that play a crucial role in the digestion and absorption of nutrients, including vitamin B12. 

Changes in the gut microbiome induced by metformin can affect the absorption of B12, leading to reduced uptake.

Inhibition of Calcium-Dependent Membrane Action

Metformin can impair calcium-dependent membrane action in the cells that line the small intestine. 

This action is essential for the proper absorption of vitamin B12. By interfering with this process, metformin can hinder the body’s ability to take up B12 from the food we consume.

Alteration of the Intrinsic Factor

The intrinsic factor is a glycoprotein produced by the stomach’s parietal cells and is vital for the absorption of vitamin B12. Metformin may impact the production and secretion of the intrinsic factor, leading to impaired B12 absorption.

The Clinical Implications

The potential link between metformin and vitamin B12 deficiency raises important clinical considerations. Vitamin B12 deficiency can manifest in various ways, including:


A deficiency of B12 can lead to anemia, which may present as fatigue, weakness, and pale skin.

Neurological Symptoms

Nerve damage due to B12 deficiency can cause neurological symptoms such as numbness, tingling, and difficulty with coordination.

Mood Changes

Some individuals may experience mood changes, depression, or memory problems: B12 deficiency can lead to digestive problems, including diarrhea and constipation.

Monitoring and Mitigation

The potential for metformin to induce vitamin B12 deficiency has led to a growing interest in monitoring B12 levels in individuals taking the medication. 

Routine testing of vitamin B12 status is advisable for those on long-term metformin therapy, especially for individuals in the higher-risk categories mentioned earlier. 

Dietary Modification

Increasing the consumption of B12-rich foods, such as meat, fish, eggs, and dairy products, or taking B12 supplements.


Vitamin B12 supplements, available in various forms (oral or injections), can help address deficiencies. The choice of supplementation method depends on the severity of the deficiency and individual needs.

Medication Adjustment

In some cases, healthcare providers may consider adjusting the metformin dosage or exploring alternative diabetes management strategies. However, this should be carefully evaluated, taking into account the patient’s overall health and diabetes control.

Regular Monitoring

Continued monitoring of vitamin B12 levels is essential to ensure that any interventions are effective in maintaining adequate B12 status.

The Balancing Act

While the association between metformin and vitamin B12 deficiency is a noteworthy concern, it’s essential to recognize that metformin remains a vital and effective tool in managing type 2 diabetes. 

The benefits of improved blood sugar control often outweigh the potential risks associated with B12 deficiency, especially when patients and healthcare providers work together to mitigate these risks.

Patients taking metformin should have open and honest discussions with their healthcare providers about their specific risk factors and individualized care plans. 

For the majority of people, the Recommended Dietary Allowance (RDA) for vitamin B12 is 2.4 micrograms (mcg) per day for adults. 

However, individuals with diabetes may have unique considerations that affect their B12 requirements. In this discussion, we’ll explore these considerations and provide guidance on vitamin B12 intake for diabetics.

Factors Affecting Vitamin B12 Requirements

As people age, their ability to absorb B12 from food decreases. This is why older adults often have higher B12 requirements.

Vegans and vegetarians may be at higher risk of B12 deficiency because animal products are the primary dietary sources of B12. Those following plant-based diets should pay extra attention to their B12 intake.

Certain gastrointestinal conditions, such as celiac disease or atrophic gastritis, can impair the absorption of B12 from food, making supplementation necessary for some individuals.

Some medications, such as proton pump inhibitors (PPIs) or H2 receptor antagonists, can reduce stomach acid production and affect B12 absorption.

How Much Vitamin B12 Should A Diabetic Take?

How Much Vitamin B12 Should A Diabetic Take

For individuals with dietary restrictions, there are B12-fortified foods available, such as certain breakfast cereals, plant-based milk alternatives, and nutritional yeast. 

However, it’s important to carefully read labels to ensure that the fortified products provide an adequate amount of B12.

B12 Supplements for Diabetics

In cases where dietary sources are insufficient or malabsorption is a concern, B12 supplements are a reliable way to meet the body’s requirements. Supplements are available in various forms, including oral supplements, sublingual tablets, and B12 injections.

Here are some key considerations for diabetics when it comes to B12 supplementation:

Consult a Healthcare Provider

Before starting any supplementation, especially if you have diabetes or other underlying health conditions, it’s crucial to consult with your healthcare provider. 

They can assess your B12 status, discuss your dietary habits, and recommend the appropriate form and dosage of B12 supplementation.

Regular Monitoring

If you’re taking metformin or have other risk factors for B12 deficiency, your healthcare provider may recommend regular monitoring of your B12 levels to ensure that supplementation is effectively maintaining your B12 status within the desired range.

Sublingual B12

Sublingual B12 tablets are dissolved under the tongue and may be a suitable option for individuals with absorption issues in the gastrointestinal tract.


In severe cases of deficiency or when malabsorption is a significant concern, healthcare providers may recommend B12 injections, which deliver the vitamin directly into the bloodstream.

Why Does Metformin Cause Lactic Acidosis?

Why Does Metformin Cause Lactic Acidosis

Metformin is a widely prescribed medication for the management of type 2 diabetes, but it is associated with a rare but serious side effect known as lactic acidosis. 

Lactic acidosis is a potentially life-threatening condition characterized by the accumulation of lactic acid in the bloodstream. Understanding why metformin can cause lactic acidosis is essential for both healthcare providers and individuals taking this medication.

Altered Cellular Metabolism

Metformin primarily works by reducing the production of glucose in the liver and enhancing insulin sensitivity in peripheral tissues. It does so by inhibiting a complex called mitochondrial respiratory chain complex I in the mitochondria of liver cells. 

This inhibition decreases the energy production through oxidative phosphorylation in the mitochondria, leading to a shift in cellular metabolism.

Normally, under aerobic conditions, glucose is metabolized to carbon dioxide and water, producing energy in the form of adenosine triphosphate (ATP). 

In the absence of adequate ATP production, cells can shift towards anaerobic metabolism, where glucose is metabolized to lactate (lactic acid) instead of carbon dioxide and water. This increase in lactate production can contribute to lactic acidosis.

Accumulation of Lactate

Lactate is a normal byproduct of glucose metabolism and is typically cleared from the bloodstream by the liver and other tissues. 

However, when metformin reduces mitochondrial oxidative phosphorylation and disrupts the balance between lactate production and clearance, lactate can accumulate in the blood.

Impaired Lactate Clearance

Metformin may also impair the body’s ability to clear lactate from the bloodstream. In some cases, it may affect the uptake of lactate by the liver, which is a key organ for lactate clearance. 

This disruption in lactate handling, combined with increased lactate production, can lead to elevated lactate levels.

Predisposing Factors

It’s important to note that lactic acidosis associated with metformin use is rare and is often linked to specific predisposing factors, such as impaired kidney function. 

Metformin is primarily excreted through the kidneys, and when kidney function is compromised, metformin can accumulate in the bloodstream, increasing the risk of lactic acidosis.

Dehydration and Other Medical Conditions

Dehydration and certain medical conditions, such as heart failure, sepsis, and respiratory failure, can further elevate the risk of lactic acidosis when combined with metformin use. 

These conditions can reduce oxygen delivery to tissues and impair lactate clearance, exacerbating the problem.


What are the common symptoms of vitamin B12 deficiency?

Common symptoms of vitamin B12 deficiency include fatigue, weakness, pale skin, shortness of breath, dizziness, and heart palpitations. Neurological symptoms can also occur, such as numbness and tingling in the hands and feet, difficulty walking, and memory problems. 

How is vitamin B12 deficiency diagnosed?

Diagnosis typically involves a blood test to measure the level of vitamin B12 in the blood. In addition to this, a healthcare provider may perform other tests, such as a complete blood count (CBC) to check for anemia and a peripheral blood smear to examine the appearance of red blood cells. 

Can vitamin B12 deficiency be prevented through diet alone?

Yes, a well-balanced diet can help prevent B12 deficiency. Consuming B12-rich foods such as meat, fish, dairy, and eggs can provide an adequate intake for most individuals. 

What is the recommended treatment for vitamin B12 deficiency?

The treatment for B12 deficiency depends on its cause and severity. For individuals with dietary insufficiency, increasing B12 intake through diet or supplements is usually effective. 

Are there any long-term complications associated with untreated vitamin B12 deficiency?

Yes, untreated vitamin B12 deficiency can lead to long-term complications. Some of these complications include irreversible neurological damage, especially in severe cases. Anemia can persist, causing ongoing fatigue and weakness. 


The connection between metformin and vitamin B12 deficiency is a complex issue that warrants attention and consideration, especially for those with diabetes who rely on this medication for glucose control. 

Metformin’s interference with the absorption of vitamin B12 is primarily attributed to its effects on the gastrointestinal system, where it disrupts the balance of gut bacteria and the production of intrinsic factor, a crucial factor in B12 absorption.

Awareness of this potential side effect is vital for healthcare providers and patients alike, as untreated vitamin B12 deficiency can lead to an array of health problems, including anemia and neurological issues. 

Regular monitoring of vitamin B12 levels, dietary modifications, and even supplementation may be necessary to counteract this risk, ensuring that the benefits of metformin therapy are not overshadowed by unintended consequences.

Leave a Comment

Dear Seniors 


Please subscribe to our newsletters